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1.
Pathologica ; 1(1): 148-154, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37216303

RESUMEN

Background: Hydatidiform moles (HM) are members of gestational trophoblastic diseases (GTD) and, in some cases, might progress to gestational trophoblastic neoplasia (GTN). HMs are either partial (PHM) or complete (CHM). Some HMs are challenging in arriving at a precise histopathological diagnosis. This study aims to investigate the expression of BCL-2 by immunohistochemistry (IHC) in HMs as well as in normal trophoblastic tissues "products of conception (POC) and placentas" using Tissue MicroArray (TMA) technique. Methods: TMAs were constructed using the archival material of 237 HMs (95 PHM and 142 CHM) and 202 control normal trophoblastic tissues; POC and unremarkable placentas. Sections were immunohistochemically stained using antibodies against BCL-2. The staining was assessed semi-quantatively (intensity and percentage of the positive cells) in different cellular components (trophoblasts and stromal cells). Results: BCL-2 showed cytoplasmic expression in more than 95% of trophoblasts of PHM, CHM and controls. The staining showed a significant reduction of the intensity from controls (73.7%), PHMs (76.3%) to CHM (26.9%). There was a statistically significant difference between PHM and CHM in the intensity (p-value 0.0005) and the overall scores (p-value 0.0005), but not the percentage score (p-value > 0.05). No significant difference was observed in the positivity of the villous stromal cells between the different groups. All cellular components were visible using the TMA model of two spots/case (3 mm diameter, each) in more than 90% of cases. Conclusions: Decreased BCL-2 expression in CHM compared to PHM and normal trophoblasts indicates increased apoptosis and uncontrolled trophoblastic proliferation. Construction of TMA in duplicates using cores of 3 mm diameter can overcome tissue heterogeneity of complex lesions.


Asunto(s)
Mola Hidatiforme , Neoplasias Uterinas , Embarazo , Femenino , Humanos , Neoplasias Uterinas/diagnóstico , Mola Hidatiforme/genética , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2 , Inmunohistoquímica
2.
J Indian Assoc Pediatr Surg ; 24(3): 180-184, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31258266

RESUMEN

INTRODUCTION: Laparoscopic splenectomy (LS) became the standard choice for splenectomy in children with benign hematological disease. There are few reports about pancreatic injury during LS. The purpose of this study is to spot on factors increasing the risk of pancreatic injury during LS in children. PATIENTS AND METHODS: A total of 140 children had LS for benign causes. Children were categorized into A and B groups. LigaSure™ was used to control pedicle in Group A, while endoscopic staplers were used in Group B. Preoperative levels of amylase, lipase, and lactate dehydrogenase (LDH) were obtained. The mean of pancreatic enzymes and LDH values was calculated on the 3 postoperative successive days. RESULTS: A total of 71 boys and 69 girls had LS. The mean splenic size was 13.50 cm in Group A and 12.51 cm in Group B. The mean operative time in Group A was 41.91 min and in Group B was 56.36 min. The mean level of amylase was 42.99 IU/ml in Group A and 75.70 IU/ml in Group B (P = 0.001). The mean level of lipase was 37 IU/ml in Group A and 76.66 IU/ml in Group B (P = 0.001). CONCLUSION: Pancreatic injury during LS is a rare complication usually presented on biochemical level. We believe that it is a hemostatic-dependent complication rather than splenic size or nature of disease.

3.
Int J Cancer ; 138(3): 652-63, 2016 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-26311411

RESUMEN

Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density.


Asunto(s)
Adenocarcinoma/irrigación sanguínea , Proteínas de Unión al Calcio/fisiología , Carcinoma Ductal Pancreático/irrigación sanguínea , Proteínas de la Membrana/fisiología , Proteínas Musculares/fisiología , Neovascularización Patológica/etiología , Neoplasias Pancreáticas/irrigación sanguínea , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Proteínas de Unión al Calcio/análisis , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Proliferación Celular , Humanos , Proteínas de la Membrana/análisis , Proteínas Musculares/análisis , Neoplasias Pancreáticas/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Factor A de Crecimiento Endotelial Vascular/análisis
4.
J Biol Chem ; 288(2): 1374-84, 2013 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-23168411

RESUMEN

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophil cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted in exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted in a significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophil chemotaxis from AR patients and Eol-1 cells was mediated through the CRTH2 receptor. Cell migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition but not to tyrosine kinase or p38 MAPK inhibition or calcium chelation. Western blot demonstrated a novel CRTH2-mediated cytosol-to-membrane translocation of PKC-ε, PKC-δ, and PKA-α, -γ, and -IIαreg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils.


Asunto(s)
Eosinofilia/patología , Eosinófilos/citología , Hipersensibilidad/patología , Receptores Inmunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Tráquea/patología , Péptido Intestinal Vasoactivo/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Eosinofilia/metabolismo , Citometría de Flujo , Humanos , Hipersensibilidad/metabolismo , Inmunohistoquímica , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tráquea/metabolismo , Péptido Intestinal Vasoactivo/química
5.
Ann Diagn Pathol ; 18(1): 21-6, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24321463

RESUMEN

Breast carcinoma is a heterogeneous disease affected by patients' ethnicity. Gene expression analysis identified several molecular subtypes, and similar subtyping has now been found to be feasible using immunohistochemistry. This study estimated the distribution of intrinsic breast cancer subtypes using estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (Her2/neu), and cytokeratin 5/6 immunostaining in a cohort of 125 Egyptian women diagnosed as having invasive breast carcinoma. Associations with clinicopathologic variables and the prognostic markers Bcl-2 and Cyclin D1 were investigated and statistically analyzed. Population difference in breast cancer subtypes was detected, suggesting etiologic and genetic heterogeneity among demographic groups. As reported worldwide, most tumors were luminal A (39.2%), but basal-like and unclassified subtypes had higher proportions among our cohort (16.8% and 16%, respectively), particularly in premenopausal patients (P = .0001), in contrast to postmenopausal African Americans, premenopausal European Americans, and other populations. Her2-overexpressing subtype was the least common subtype (13.65%) among our patients, although it is more common in Asians. Basal-like and unclassified carcinomas were more frequently grade 3 neoplasms (P = .035). Lobular histology was distributed among luminal A, B and unclassified subtypes (P = .006). The highest frequency of nodal positivity was associated with Her2 overexpressing carcinomas (94.1%, P = .0001). Luminal and unclassified carcinomas more likely expressed Bcl-2 (P = .011) and Cyclin D1 (P = .0001), whereas basal and Her2 subtypes had the lowest expression levels. Immunohistochemistry-based subtyping can be helpful in separating breast carcinoma into subtypes that vary in distribution among different populations. These subtypes have distinct clinicopathologic features and diverse prognostication, which may imply different therapeutic options for each subtype.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Carcinoma/clasificación , Carcinoma/patología , Adulto , Neoplasias de la Mama/metabolismo , Carcinoma/metabolismo , Egipto , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Receptor ErbB-2/análisis , Receptor ErbB-2/biosíntesis
6.
J Egypt Natl Canc Inst ; 35(1): 26, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37599312

RESUMEN

AIMS: Both S100A4 and Glypican-3 have been known to be engaged in HCC development and progression. This study aimed to evaluate both S100A4 and GPC3 expression in HCC tissues as a prognostic markers. METHODS: Tissues from 70 patients of HCC in cirrhotic HCV patients were evaluated by immunohistochemistry using antibodies against SA100A4 and GPC3 and compared with tumor-adjacent tissue (controls). All cases were followed for 40 months. RESULTS: GPC3 was more expressed in HCC (79%) than S100A4 (21%). S100A4 was more significantly expressed in cases showing metastasis, microscopic vascular emboli, necrosis, and grade III tumors. There was no relationship between overall survival and both S100A4 and GPC3. The only significant independent predictor for recurrence was decompensation (OR 3.037), while metastasis was significantly predicted by S100A4 expression (OR 9.63) and necrosis (OR 8.33). CONCLUSION: S100A4 might be used as a prognostic marker for HCC, while GPC3 is a reliable marker of HCC diagnosis.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Pronóstico , Glipicanos , Neoplasias Hepáticas/diagnóstico , Necrosis , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Hepatitis C/complicaciones , Proteína de Unión al Calcio S100A4/genética
7.
Maedica (Bucur) ; 18(1): 27-34, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37266479

RESUMEN

Background and objectives: Assessment of HER2 gene status has central role in the management of breast cancer patients. For determining HER2 status, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the most commonly used tests. Immunohistochemistry scores of 3+ and 1+ were considered as HER2 positive and negative, respectively. On the other hand, HER2 equivocal cases need further confirmation by FISH test assessment. This study aimed to identify the clinicopathological characteristics of patients with HER2 equivocal tumors served by Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, with emphasis on treatment plans and disease outcome. Methods: This was a retrospective cross-sectional study, which involved all breast cancer female patients who were referred to SQUH from 2016 to 2020. It included a total of 108 patients who were diagnosed with HER2 (2+) breast cancer. Patients' data were analyzed in relation to the subsequent FISH status. Results: During the study period, data from 108 females with HER2 2+ were collected; among them, 22 (20%) were FISH positive, 64 (59%) FISH negative, 17 (16%) FISH borderline and five (5%) with no results. Regarding patients' characteristics, 91.2% of all subjects had invasive ductal carcinoma, 93.2% expressed estrogen receptors and 77.6% progesterone receptor. Age, postmenopausal histopathology, tumor grade, TNM staging, ER, PR, Ki67, LVSI, NLR, treatment and follow-up did not show significant association with different FISH results. Conclusions: The majority of HER2 equivocal breast cancer cases were FISH negative. In trastuzumab chemotherapy, an association between different FISH results was expected.

8.
Eur J Obstet Gynecol Reprod Biol X ; 16: 100172, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36440057

RESUMEN

Background: Endometrial carcinoma (EC) is the most common gynaecological cancer worldwide. The Cancer Genome Atlas molecular grouping of a given case of EC could be assessed by POLE gene mutation, mismatch repair (MMR) 'to reflect microsatellite instability' and p53 status, which has proved to be of prognostic value. Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) are playing a progressively important role in tumour immunology and cancer treatment. Objectives: To investigate PD-L1 immunohistochemical expression in EC in relation to MMR and p53 status. Associations between marker expression and different histopathological parameters were also investigated. Methods: This retrospective study was performed on archival biopsies of 170 cases of EC using a tissue microarray model. Immunohistochemical staining was applied using antibodies against PD-L1, MLH1, MSH2 and p53. Results: The percentages of positivity were as follows: PD-L1, 19.6%; MLH1, 79.5%; MSH2, 78.5%; and p53 mutant, 13.8%. There was significant correlation between MLH1 expression and MSH2 expression (p = 0.008). Tumour grade was significantly correlated with stage (p = 0.005) and p53 mutant expression (p = 0.008). Combined PD-L1 positivity and MMR deficiency showed significant correlation with the presence of lymphovascular space invasion (p = 0.014). MSH2 negativity was significantly associated with poorer overall survival (p = 0.014). Conclusions: A panel of immunohistochemical markers (PD-L1, MLH1, MSH2 and p53) could help to predict the prognosis and plan the treatment of patients with EC. MMR deficiency seems to be a good predictor for PD-L1 status, and therefore the response to potential PD-1/PD-L1 inhibitor therapy.

9.
J Oncol Pharm Pract ; 17(2): 119-24, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20015931

RESUMEN

BACKGROUND: Breast cancer is the most common malignancy among females worldwide. Molecular analysis of p53 is likely to have value in diagnosis, prognosis, and treatment of breast cancer. OBJECTIVE: To study the frequency and spectrum of p53 gene mutations in breast cancer patients residing Al Dakahliya district in the north of Egypt. MATERIALS AND METHODS: Thirty patients with cancer breast as well as 10 controls were evaluated for p53 status by flow-cytometry, PCR-SSCP, and sequencing analysis. RESULTS: P53 mutations were evident in five breast cancer patients (17%) including two missense mutations (A218 T and R279 G) in exon 6, 8; nonsense mutations (S297stop and Y159stop) in exon 8, 5, respectively, and frame shift mutation (M133 fs) in exon 5. p53 mutations were associated with invasive ductal carcinoma, large tumor size, and advanced disease stage CONCLUSION: p53 gene mutations is potentially responsible for pathogenesis and clinical aggressiveness of breast cancer in our locality.


Asunto(s)
Neoplasias de la Mama/genética , Genes p53 , Mutación , Polimorfismo Conformacional Retorcido-Simple , Adulto , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patología , Codón sin Sentido , Análisis Mutacional de ADN , Egipto , Exones , Femenino , Mutación del Sistema de Lectura , Estudios de Asociación Genética , Humanos , Persona de Mediana Edad , Mutación Missense , Invasividad Neoplásica/genética , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Carga Tumoral , Proteína p53 Supresora de Tumor/metabolismo
10.
Maedica (Bucur) ; 16(4): 634-641, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35261666

RESUMEN

Objectives:This study is aiming to assess the diagnostic value of p16 immunohistochemistry (IHC) for a variety of epithelial lesions in the service provided by the Department of Pathology at Sultan Qaboos University Hospital (SQUH), Sultanate of Oman. This study would enhance pathologists' ability to diagnose and differentiate between different types of epithelial lesions reliably. Methods:This study is a retrospective observational cross-sectional study. A total of 117 immunohistochemical tests for p16 were collected from the pathology lab at SQUH from January 2010 to December 2020. Data was analyzed using SPSS software. For numerical data, mean and percentages were used. For measuring the association between different pathological and clinical findings, the categorized variables were analyzed using the chi-square test. Results:Immunohistochemistry of p16 was mainly used to diagnose uterine cervical, ovarian, oropharyngeal and anal epithelial lesions. Predominately, it was applied on cervical intraepithelial neoplasia grades 1, 2 and 3 (CIN I, II, III), squamous metaplasia, chronic cervicitis, anal intraepithelial neoplasia as well as different types of squamous cell carcinoma, adenocarcinoma, and serous carcinoma. Conclusion:The results of the present study revealed the wide application of p16 IHC as a marker to reach the final histopathological diagnosis of epithelial lesions in the pathology lab at SQUH. The marker can be used effectively to differentiate between different types of lesions showing similar appearance on hematoxylin and eosin stain.

11.
Maedica (Bucur) ; 16(4): 734-737, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35261680

RESUMEN

Patients with Swyer syndrome, "XY gonadal dysgenesis", have fibrosed gonads with a significant risk of developing germ cell tumours. During radiological assessment, a 17-year-old female with Swyer syndrome showed mildly enlarged gonads that were removed laparoscopically and proved pathologically to be bilateral gonadoblastomas. In addition, the right sided lesion showed overgrowth by dysgerminoma. The patient was further treated with combination chemotherapy and she was in complete remission for three years.

12.
Immunol Res ; 68(6): 389-397, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32939649

RESUMEN

Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 have crucial role in the pathogenesis of endometriosis. In this study, we investigated the immune-modulatory role of humanized anti-IL-6 receptor monoclonal antibodies in the treatment of endometriosis. This is a prospective, randomized, controlled, blinded study in which Sprague Dawley rats were used as animal model of endometriosis. Animals were randomly divided into two groups, a test group which received tocilizumab (Actemra; Roche, Switzerland) and a control group which received saline. Afterwards, a comparison was done between the eutopic and ectopic endometrium that was excised from both groups, histopathologically and immune-histochemically. Histopathologic assessment and immune-histochemical staining were performed using antibodies against IL-6. Tocilizumab significantly suppressed the volume of endometriotic lesions compared with non-treated rats (P = 0.006) and atrophied the ectopic endometrial-like epithelium (in 42.8% of treated rats vs 0% in the control group). Tocilizumab also decreased the anti-IL-6 receptor immune-histochemical staining intensity in ectopic endometrium (from non to +++ in the test group vs ++ or more in the control group), with no apparent difference in the eutopic one reflecting the down-regulation of IL-6-producing cells in ectopic endometriotic lesions. In rats with induced endometriosis, anti-IL-6 receptor monoclonal antibodies could offer a new horizon of usage of this immune-modulatory biologic drug, used in other autoimmune diseases, in treatment of endometriosis.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Endometriosis/tratamiento farmacológico , Endometriosis/patología , Receptores de Interleucina-6/antagonistas & inhibidores , Animales , Biomarcadores , Endometriosis/etiología , Femenino , Inmunohistoquímica , Ratas , Ratas Sprague-Dawley
13.
Cancer Immunol Immunother ; 58(4): 603-14, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18802697

RESUMEN

Although human papillomavirus (HPV) DNA is detected in the majority of squamous intraepithelial lesions (SIL) and carcinoma (SCC) of the uterine cervix, the persistence or progression of cervical lesions suggest that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most SIL show quantitative and functional alterations of Langerhans cells (LC). The aim of this study was to determine whether prostaglandins (PG) may affect LC density in the cervical (pre)neoplastic epithelium. We first demonstrated that the epithelial expression of PGE(2) enzymatic pathways, including cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1), is higher in SIL and SCC compared to the normal exocervical epithelium and inversely correlated to the density of CD1a-positive LC. By using cell migration assays, we next showed that the motility of immature dendritic cells (DC) and DC partially differentiated in vitro in the presence of PGE(2) are differentially affected by PGE(2). Immature DC had a lower ability to migrate in the presence of PGE(2) compared to DC generated in vitro in the presence of PGE(2). Finally, we showed that PGE(2) induced a cytokine production profile and phenotypical features of tolerogenic DC, suggesting that the altered expression of PGE(2) enzymatic pathways may promote the cervical carcinogenesis by favouring (pre)cancer immunotolerance.


Asunto(s)
Dinoprostona/biosíntesis , Tolerancia Inmunológica/inmunología , Células de Langerhans/inmunología , Lesiones Precancerosas/enzimología , Displasia del Cuello del Útero/enzimología , Neoplasias del Cuello Uterino/enzimología , Antígenos Virales/inmunología , Western Blotting , Diferenciación Celular/inmunología , Movimiento Celular/inmunología , Ensayo de Inmunoadsorción Enzimática , Epitelio/inmunología , Femenino , Humanos , Inmunohistoquímica , Células de Langerhans/citología , Papillomaviridae/inmunología , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/virología , Transducción de Señal/fisiología , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/inmunología , Displasia del Cuello del Útero/virología
14.
Obstet Gynecol ; 133(5): 1024-1031, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30969220

RESUMEN

OBJECTIVE: To investigate the effect of second uterine curettage on the number of chemotherapy courses and relapse rate in low-risk postmolar gestational trophoblastic neoplasia. METHODS: In a phase III trial, patients with low risk gestational trophoblastic neoplasia were randomised (1:1) to a second curettage or no curettage group before methotrexate treatment. Eligibility criteria were serum human chorionic gonadotropin (hCG) level 5,000 international units/L or less and fit for treatment with methotrexate. Exclusion criteria were previous uterine perforation and life-threatening bleeding. With a two-sided 5% significance level and a power of 99%, a sample size of 44 patients per group was necessary to detect a mean reduction in 2.3 chemotherapy courses. The primary outcome was the number of chemotherapy courses required for hCG normalization. Secondary outcomes were needed for second-line treatment, toxicity, relapse rates, and variables associated with number of chemotherapy courses. RESULTS: From October 2011 through February 2016, 89 patients entered the study at the Mansoura Trophoblastic Clinic; in each group, 43 patients were included in the intention-to-treat analyses. Surgical complications did not occur. The mean number of chemotherapy courses required to reach hCG normalization was 4.4±2.2 SD in the control group vs 3.8±2.3 SD in the intervention group (P=.14). Groups were comparable in terms of second-line treatment needed to reach hCG normalization, and relapse within the first year. Only hCG levels related to the number of chemotherapy cycles required for hCG normalization. CONCLUSION: Second uterine curettage did not reduce the number of chemotherapy courses required or affect relapse rate in patients with low-risk postmolar gestational trophoblastic neoplasia. CLINICAL TRIALS REGISTRATION: Dutch Trial Registry, NTR3390.


Asunto(s)
Legrado , Enfermedad Trofoblástica Gestacional/cirugía , Neoplasias Uterinas/cirugía , Adulto , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Terapia Combinada , Femenino , Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Humanos , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Embarazo , Resultado del Tratamiento , Neoplasias Uterinas/tratamiento farmacológico
15.
J Pathol Transl Med ; 53(3): 164-172, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30813708

RESUMEN

BACKGROUND: In order to improve the efficacy of endometrial carcinoma (EC) treatment, identifying prognostic factors for high risk patients is a high research priority. This study aimed to assess the relationships among the expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and the different histopathological prognostic parameters in EC and to assess the value of these in the management of EC. METHODS: We examined 109 cases of EC. Immunohistochemistry for ER, PR, HER2, and Ki-67 were evaluated in relation to age, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and grade, depth of infiltration, cervical and ovarian involvement, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis. RESULTS: The mean age of patients in this study was 59.8 ± 8.2 years. Low ER and PR expression scores and high Ki-67 expression showed highly significant associations with non-endometrioid histology (p = .007, p < .001, and p < .001, respectively) and poor differentiation (p = .007, p < .001, and p <. 001, respectively). Low PR score showed a significant association with advanced stage (p = .009). Low ER score was highly associated with LVSI (p = .006), and low PR scores were associated significantly with LN metastasis (p = .026). HER2 expression was significantly related to advanced stages (p = .04), increased depth of infiltration (p = .02), LVSI (p = .017), ovarian involvement (p = .038), and LN metastasis (p = .038). There was a close relationship between HER2 expression and uterine cervical involvement (p = .009). Higher Ki-67 values were associated with LN involvement (p = .012). CONCLUSIONS: The over-expression of HER2 and Ki-67 and low expression of ER and PR indicate a more malignant EC behavior. An immunohistochemical panel for the identification of high risk tumors can contribute significantly to prognostic assessments.

16.
BMC Cancer ; 8: 147, 2008 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-18505570

RESUMEN

BACKGROUND: The 21-kDa Vaccinia virus VH1-related (VHR) dual-specific protein phosphatase (encoded by the DUSP3 gene) plays a critical role in cell cycle progression and is itself regulated during the cell cycle. We have previously demonstrated using RNA interference that cells lacking VHR arrest in the G1 and G2 phases of the cell cycle and show signs of beginning of cell senescence. METHODS: In this report, we evaluated successfully the expression levels of VHR protein in 62 hysterectomy or conization specimens showing the various (pre) neoplastic cervical epithelial lesions and 35 additional cases of hysterectomy performed for non-cervical pathologies, from patients under 50 years of age. We used a tissue microarray and IHC technique to evaluate the expression of the VHR phosphatase. Immunofluorescence staining under confocal microscopy, Western blotting and RT-PCR methods were used to investigate the localization and expression levels of VHR. RESULTS: We report that VHR is upregulated in (pre) neoplastic lesions (squamous intraepithelial lesions; SILs) of the uterine cervix mainly in high grade SIL (H-SIL) compared to normal exocervix. In the invasive cancer, VHR is also highly expressed with nuclear localization in the majority of cells compared to normal tissue where VHR is always in the cytoplasm. We also report that this phosphatase is highly expressed in several cervix cancer cell lines such as HeLa, SiHa, CaSki, C33 and HT3 compared to primary keratinocytes. The immunofluorescence technique under confocal microscopy shows that VHR has a cytoplasmic localization in primary keratinocytes, while it localizes in both cytoplasm and nucleus of the cancer cell lines investigated. We report that the up-regulation of this phosphatase is mainly due to its post-translational stabilization in the cancer cell lines compared to primary keratinocytes rather than increases in the transcription of DUSP3 locus. CONCLUSION: These results together suggest that VHR can be considered as a new marker for cancer progression in cervix carcinoma and potential new target for anticancer therapy.


Asunto(s)
Carcinoma de Células Escamosas/enzimología , Fosfatasa 3 de Especificidad Dual/biosíntesis , Displasia del Cuello del Útero/enzimología , Neoplasias del Cuello Uterino/enzimología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Línea Celular Tumoral , Núcleo Celular/enzimología , Inducción Enzimática , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Histerectomía , Queratinocitos/enzimología , Queratinocitos/patología , Microscopía Confocal , Análisis de Secuencia por Matrices de Oligonucleótidos , Estadística como Asunto , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/cirugía
17.
Front Surg ; 5: 3, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29459898

RESUMEN

AIM: Pleomorphic adenoma is the most common benign tumor of the parotid gland and is classically treated with superficial or total parotidectomy. Less radical surgeries have been proposed to minimize the risk of facial nerve injury. The oncological safety of these procedures remains controversial. We conducted this study to evaluate the safety of superficial hemi-lobectomy (quadrantectomy). PATIENTS AND METHODS: Retrospective analysis was conducted on the paraffin sections of archived superficial parotidectomy specimens from 11 male and 6 female patients (median age 33 years). The microscopic extent of extra-capsular extension was determined on pathological revision. In addition, prospective evaluation of 12 quadrantectomy procedures (M/F = 7/5, median age = 36 years) compared to 24 radical surgeries (M = F, median age = 40 years) regarding temporary and persistent facial nerve dysfunction on routine clinical assessment and recurrence rate. RESULTS: On retrospective pathological revision, pleomorphic adenomata had a median microscopic spread of 3 mm beyond capsule in paraffin sections (SD = 3.6). On prospective analysis with a median follow-up of 33 months (range = 18-54 months), quadrantectomy had similar relative risk of temporary facial nerve dysfunction evaluated at the immediate postoperative period as well as persistent nerve dysfunction assessed at 3 months (P = 0.701 and P = 0.902, respectively). Of the whole study population, one case of recurrence after total parotidectomy was observed at mid-term follow-up (P = 1.000). CONCLUSION: Parotid quadrantectomy is a safe management for smaller pleomorphic adenomata localized close to one of the two divisions of the facial nerve.

19.
J Pathol Transl Med ; 51(4): 381-387, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28607326

RESUMEN

BACKGROUND: Although the morphological features characteristic of products of conception specimens including molar pregnancies are well described, substantial histopathological similarities are observed between the different entities, especially in cases of early pregnancies. Furthermore, there are no current solid criteria that could predict cases with progression to persistent gestational trophoblastic disease. In this study, we aimed to determine the most specific histopathological and immunohistochemical features required for accurate diagnosis that can reliably predict the clinical behavior. METHODS: Sixty-five cases of products of conception were reviewed clinically and pathologically, and any progression to persistent gestational trophoblastic disease (GTD), if present, was noted. Pathological assessment of the archival material included re-cut sections of 5 µm in thickness, routine staining with hematoxylin and eosin and immunohistochemical staining of p57Kip2. RESULTS: Certain histopathological criteria were found to be significant in differentiation between complete hydatidiform mole (CHM) and partial hydatidiform mole including villous shape and outline, villous trophoblast hyperplasia, and atypia in extravillous trophoblasts. There were no significant differences in any morphological or immunohistochemical features between cases with or without subsequent development of GTD. CONCLUSIONS: Histopathological diagnosis of molar pregnancy remains problematic especially in early gestation. Their diagnosis should be stated after a constellation of specific histopathological criteria in order not to miss CHM. p57Kip2 immunohistochemistry is of great value in diagnosis of cases that had equivocal morphology by histopathological examination. However, there were no significant features to predict cases that subsequently developed persistent GTD.

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